Integrated sample processing devices

ABSTRACT

Sample processing devices may include compression structures that provide for the transfer of force from a platen to a platform such as a thermal block on which the sample processing device is located during processing. The sample processing devices may include a fill reservoir structure with various features such as arcuate edges, radially aligned exit channels, support structures, and selectively variable heights with a corresponding variable volume distribution.

BACKGROUND

[0001] Modern scientific investigations frequently involve the use oflarge number of chemical reactions. For efficient implementation, thesereactions are preferably run using systems that minimize setup times andcost while ensuring the quality of their results.

[0002] In many cases, a multiplicity of reactions are performed onsystems in which a small set of reactants are combined with a muchlarger set of reactants. For example, a single biological sample may besubjected to a multiplicity of polymerase chain reactions, each of whichaddress the expression level of a single gene.

[0003] Many different chemical, biochemical, and other reactions arealso sensitive to small temperature variations. The reactions may beenhanced or inhibited based on the temperatures of the materialsinvolved. In many such reactions, a temperature variation of even 1 or 2degrees Celsius may have a significantly adverse impact on the reaction.Although it may be possible to process samples individually and obtainaccurate sample-to-sample results, individual processing can betime-consuming and expensive.

[0004] One approach to reducing the time and cost of processing multiplesamples is to use a device including multiple chambers in whichdifferent portions of one sample or different samples can be processedsimultaneously. However, this approach presents several temperaturecontrol related issues. When using multiple chambers, the temperatureuniformity from chamber to chamber may be difficult to control. Anotherproblem involves the speed or rate at which temperature transitionsoccur when thermal processing, such as when thermal cycling. Stillanother problem is the overall length of time required to thermal cyclea sample(s).

[0005] The multiple chamber device may include a distribution system.However, the distribution system presents the potential forcross-contamination. Sample may inadvertently flow among the chambersduring processing, thereby potentially adversely impacting thereaction(s) occurring in the chambers. This may be particularlysignificant when multiple samples are being processed. In addition, thedistribution system may present problems when smaller than usual samplesare available, because the distribution system is in fluid communicationwith all of the process chambers. As a result, it is typically notpossible to prevent delivery of sample materials to all of the processchambers to adapt to the smaller volume samples.

[0006] Thermal processing, in and of itself, presents an issue in thatthe materials used in the devices may need to be robust enough towithstand repeated temperature cycles during, e.g., thermal cyclingprocesses such as PCR. The robustness of the devices may be moreimportant when the device uses a sealed or closed system. Also, it isoften required that the process chambers remain in adequate alignmentwith instrument optics despite temperature changes and the attendantthermal expansion.

[0007] Various sample processing devices of the present invention aredescribed in U.S. Provisional Patent Application Serial No. 60/214,508filed on Jun. 28, 2000 and titled THERMAL PROCESSING DEVICES AND METHODS(Attorney Docket No. 55265USA19.003); U.S. Provisional PatentApplication Serial No. 60/214,642 filed on Jun. 28, 2000 and titledSAMPLE PROCESSING DEVICES, SYSTEMS AND METHODS (Attorney Docket No.55266USA99.003); U.S. Provisional Patent Application Serial No.60/237,072 filed on Oct. 2, 2000 and titled SAMPLE PROCESSING DEVICES,SYSTEMS AND METHODS (Attorney Docket No. 56047USA29); U.S. patentapplication Ser. No. 09/710,184, filed Nov. 10, 2000, titled CENTRIFUGALFILLING OF SAMPLE PROCESSING DEVICES (Attorney Docket No.55265USA9A.002), U.S. patent application Ser. No. 09/895,001, filed Jun.28, 2001, and titled SAMPLE PROCESSING DEVICES AND CARRIERS; U.S. patentapplication Ser. No. 09/895,010, filed Jun. 28, 2001, and titled SAMPLEPROCESSING DEVICES.

[0008] The documents identified above all disclose a variety ofdifferent constructions of sample processing devices that could be usedto manufacture sample processing devices according to the principles ofthe present invention. For example, although many of the sampleprocessing devices described herein are attached using adhesives (e.g.,pressure sensitive adhesives), devices of the present invention could bemanufactured using heat sealing or other bonding techniques.

[0009] Although the devices and their carriers identified in theabove-listed patent documents may provide many advantages over the priorart, further improvements may still be possible. For example, the use ofa carrier separate from the sample processing device may add cost to thesample processing devices as delivered to customers because of the needto manufacture different components separately from each other and thenaccurately assemble the components. In addition to adding cost,inaccurate assembly may cause performance problems due to misalignmentof interrogation zones with the optics train of the analytical device.Further variability in the assembly process may induce unwantedpart-to-part variability in the way the assembly fits to the thermalplaten and hence thermal variations between process chambers.

SUMMARY OF THE INVENTION

[0010] The present invention provides integrated sample processingdevices for thermal processing of multiple samples at the same time. Thesample processing devices may include compression structures thatprovide for the transfer of force from a platen to a thermal block onwhich the sample processing device is located during processing. Bydistributing the compression structures over a compliant sampleprocessing device, intimate contact between substantially all of theprocessing chambers in the sample processing device and the thermalblock can be achieved in spite of variations in the thickness of thesample processing device due to, e.g., manufacturing tolerances.

[0011] Such compression structures may also be useful in ensuring thatthe reaction chambers of the sample processing device are located on acommon plane during optical interrogations performed during, or after,thermal or other processing. For example, the sample processing devicesmay be thermally processed and then placed on an optical detectionsystem for assessment of reaction products. This situation isencountered when performing “end-point reads” following thermal-cyclingon Peltier blocks that do not provide for real-time monitoring of theprocessing, e.g., PCR.

[0012] In some embodiments, the compression structures may includepermanently deformable compression structures that may help toequilibrate the force with which the processing chambers of the sampleprocessing device are urged against a platen. The permanently deformablestructures may include, e.g., frangible elements that permanently deformin a manner that provides an indication that a sample processing devicehas been used. The frangible element may, in some instances, include achromic indicator that changes color when deformed to further enhanceunaided visual determination of use of the sample processing device.

[0013] The sample processing devices may include a fill reservoirstructure with various features such as arcuate edges, radially alignedexit channels, support structures, and selectively variable heights (andcorresponding volume distribution) to enhance even distribution of fluidsample materials to the main channels and processing chambers of asample processing device according to the present invention.

[0014] The sample processing devices of the present invention preferablyhave a form factor that is compatible with conventional microtiterplates such that conventional microtiter plate processing equipment andsystems may be used to process sample processing devices of the presentinvention. For example, it may be preferred that that the sampleprocessing devices have a height of five millimeters or more.Furthermore, it may be preferred that that the sample processing devicesof the present invention have a maximum height as defined by the Societyfor Biomolecular Screening Standard “SBS-2 for Microplates HeightDimensions” (May 9, 2002).

[0015] A further advantage of the present invention may come from moreprecise control of fill port locations. The use of multiple fill portson a sample processing device is particularly advantageous if the fillports are compatible with standard laboratory robotic equipment forliquid dispensing. For example, eight or more micropipettes arefrequently arranged in a linear array with uniform spacing toefficiently fill standard microplates. Use of such micropipette arraysto fill particular embodiments of the present invention could provide asignificant benefit to users requiring highly automated laboratoryoperations using existing equipment.

[0016] Use of the present invention with such automated operations isfurther facilitated if the particular embodiment complies with thestandardized form-factor for microplates. In such cases, the handling ofthe microplate subsequent to loading can be performed by commonlyavailable robotic equipment.

[0017] Finally, because many of the reactants used with the presentinvention are often expensive and available only in small quantities, itis important to utilize sample processing devices which minimize theamounts of samples necessary to achieve satisfactory results. Inparticular, this requires loading mechanisms which efficientlydistribute the sample to each of the reaction chambers and that reducethe risk of spillage during loading and handling of the devices.

[0018] In some embodiments, the sample processing devices may includemultiple parallel fill reservoirs that are in fluid communication witheach other through a fluid path.

[0019] Methods of using such sample processing devices may includeoccluding those fluid paths to isolate the fill reservoirs aftermanufacturing the sample processing devices. The fill reservoirs maypreferably have fill ports proximate the outermost edges of the sampleprocessing device such that a sample processing device including fillreservoirs filled with sample materials may be stood on edge withoutleaking the sample materials from the fill reservoirs.

[0020] The sample processing devices of the present invention may alsoinclude deformable seals to occlude channels used to distribute samplematerials from the fill reservoirs to the process chambers. Deformableseals may also provide for isolation of the process chambers locatedalong the channels, such that chemical cross-contamination (e.g.,migration of reagents or reaction products between process chambersafter introduction of sample material) may be reduced or eliminated,particularly during sample processing, e.g. thermal cycling. Deformableseals may also provide the opportunity to tailor the devices forspecific test protocols by closing the channels leading to selectedprocess chambers before distributing sample materials. Alternatively,some deformable seals may be closed to adjust for smaller samplematerial volumes reducing the number of process chambers to which thesample materials are distributed.

[0021] It is preferred that sample processing devices of the inventionexhibit robustness in response to the rapid thermal changes that can beinduced due to the relatively high thermal conductivity and relativelylow thermal mass of the devices. This robustness may be particularlyvaluable when the devices are used in thermal cycling methods such as,e.g., PCR. In all thermal processing methods, the preferred devicesmaintain process chamber integrity despite any pressure changes that maybe associated with the temperature variations and despite thedifferences between thermal expansion rates of the various materialsused in the devices.

[0022] As used in connection with the present invention, the followingterms shall have the meanings set forth below.

[0023] “Deformable seal” (and variations thereof) means a seal that ispermanently deformable under mechanical pressure (with or without atool) to occlude a conduit along which the deformable seal is located.

[0024] “Thermal processing” (and variations thereof) means controlling(e.g., maintaining, raising, or lowering) the temperature of samplematerials to obtain desired reactions. As one form of thermalprocessing, “thermal cycling” (and variations thereof) meanssequentially changing the temperature of sample materials between two ormore temperature setpoints to obtain desired reactions. Thermal cyclingmay involve, e.g., cycling between lower and upper temperatures, cyclingbetween lower, upper, and at least one intermediate temperature, etc.

[0025] In one aspect, the present invention provides a method ofprocessing sample materials by providing a sample processing deviceincluding a body having a first major side and a second major side; abase sheet attached to the first major side of the body, and a pluralityof compression structures protruding from the second major side of thebody, wherein the body and the base sheet define one or more fillreservoirs, a plurality of process chambers, and a plurality ofchannels, wherein each channel of the plurality of channels is in fluidcommunication with at least one fill reservoir of the one or more fillreservoirs, and wherein each process chamber of the plurality of processchambers is in fluid communication with at least one channel of theplurality of channels. The method includes distributing sample materialto at least some process chambers of the plurality of process chambers;locating the base sheet of the sample processing device in contact witha thermal block; contacting the second major side of the body with aplaten to urge the base sheet of the sample processing device intointimate contact with the thermal block; and permanently deforming atleast some of the plurality of compression structures protruding fromthe second major side of the body while contacting the second major sideof the body with the platen. The temperature of the thermal block iscontrolled while the sample processing device is in contact with thethermal block.

[0026] In another aspect, the present invention provides a method ofprocessing sample materials by providing a sample processing deviceincluding a body having a first major side and a second major side; abase sheet attached to the first major side of the body, and a pluralityof compression structures protruding from the second major side of thebody, wherein the body and the base sheet define one or more fillreservoirs, a plurality of process chambers, and a plurality ofchannels, wherein each channel of the plurality of channels is in fluidcommunication with at least one fill reservoir of the one or more fillreservoirs, and wherein each process chamber of the plurality of processchambers is in fluid communication with at least one channel of theplurality of channels, and wherein the body includes a frame proximate aperimeter of the body, the frame defining a frame volume, wherein theone or more fill reservoirs are located within the frame volume. Themethod further includes distributing sample material to at least someprocess chambers of the plurality of process chambers; locating the basesheet of the sample processing device in contact with a thermal block;contacting the second major side of the body with a platen to urge thebase sheet of the sample processing device into intimate contact withthe thermal block; permanently deforming all of the compressionstructures protruding from the second major side of the body whilecontacting the second major side of the body with the platen; andcontrolling the temperature of the thermal block while the sampleprocessing device is in contact with the thermal block. Each compressionstructure of the plurality of compression structures includes a postextending from the first major surface to the second major surface ofthe body, wherein contacting the second major side of the body with aplaten to urge the base sheet of the sample processing device intointimate contact with the thermal block transfers force from the platento the thermal block. The method includes permanently deforming afrangible indicator element on at least some of the plurality ofcompression structures.

[0027] In another aspect, the present invention includes a method ofinterrogating a sample processing device by providing a sampleprocessing device including a body having a first major side and asecond major side; a base sheet attached to the first major side of thebody, and a plurality of compression structures protruding from thesecond major side of the body, wherein the body and the base sheetdefine a plurality of process chambers with sample material located inat least some process chambers of the plurality of process chambers. Themethod includes locating the base sheet of the sample processing devicein contact with an interrogation platform; contacting the second majorside of the body with a platen to urge the base sheet of the sampleprocessing device into intimate contact with the interrogation platform;permanently deforming at least some of the plurality of compressionstructures protruding from the second major side of the body whilecontacting the second major side of the body with the platen; andinterrogating at least some of the process chambers while the sampleprocessing device is in contact with the interrogation platform.

[0028] In another aspect, the present invention provides a method ofmanufacturing a sample processing device by providing a body having afirst major side and a second major side, a plurality of isolated fillreservoir structures located between the first major side of the bodyand the second major side of the body; a plurality of process chamberstructures formed into the first major side of the body; and a pluralityof channel structures formed into the first major side of the body. Themethod further includes opening a fluid path between at least one pairof adjacent isolated fill reservoir structures, wherein the number ofisolated fill reservoir structures is reduced; attaching a base sheet tothe first major side of the body, wherein the body and the base sheetdefine one or more fill reservoirs, a plurality of process chambersstructures, and a plurality of channels, wherein each channel of theplurality of channels is in fluid communication with at least one fillreservoir of the one or more fill reservoirs, and wherein each processchamber of the plurality of process chambers is in fluid communicationwith at least one channel of the plurality of channels.

[0029] In another aspect, the present invention provides a sampleprocessing device including a body having a first major side and asecond major side; one or more fill reservoir structures located betweenthe first major side of the body and the second major side of the body;a plurality of process chamber structures formed into the first majorside of the body; a plurality of channel structures formed into thefirst major side of the body; a plurality of compression structuresprotruding from the second major side of the body, wherein the pluralityof compression structures include frangible indicator elements proximatethe second major side of the body; and a base sheet attached to thefirst major side of the body, wherein the base sheet and the one or morefill reservoir structures define one or more fill reservoirs in thedevice, wherein the base sheet and the plurality of process chamberstructures define a plurality of process chambers in the device, andwherein the base sheet and the plurality of channel structures define aplurality of channels in the device, wherein each channel of theplurality of channels is in fluid communication with at least one fillreservoir of the one or more fill reservoirs, and wherein each processchamber of the plurality of process chambers is in fluid communicationwith at least one channel of the plurality of channels.

[0030] In another aspect, the present invention provides a sampleprocessing device including a fill reservoir; a plurality of processchambers; and a plurality of channels. Each channel of the plurality ofchannels is in fluid communication with the fill reservoir and eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels.The fill reservoir has an arcuate edge, wherein each channel of theplurality of channels exits the fill reservoir from the arcuate edge ofthe fill reservoir and extends in a direction normal to a tangent of thearcuate edge for a first portion of the length of the channel, andwherein the plurality of channels are aligned with a longitudinal axisfor a second portion of the length of the channel.

[0031] In another aspect, the present invention provides a sampleprocessing device having a fill reservoir; a plurality of processchambers; and a plurality of channels. Each channel of the plurality ofchannels is in fluid communication with the fill reservoir and eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels.The fill reservoir has an axis of symmetry and includes a fill portproximate the axis of symmetry, with two or more vent ports arrangedsymmetrically about the axis of symmetry.

[0032] In another aspect, the present invention provides a sampleprocessing device including a fill reservoir; a plurality of processchambers; and a plurality of channels. Each channel of the plurality ofchannels is in fluid communication with the fill reservoir and eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels.The fill reservoir includes a selectively varied height between twosides of the fill reservoir such that a desired distribution of thevolume of the fill reservoir is provided.

[0033] In another aspect, the present invention provides a sampleprocessing device including a fill reservoir; a plurality of processchambers; and a plurality of channels. Each channel of the plurality ofchannels is in fluid communication with the fill reservoir and eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels.The device further includes one or more support structures locatedwithin the fill reservoir, wherein the support structures maintainspacing between two opposing sides of the fill reservoir. The fillreservoir also includes an arcuate edge, wherein each channel of theplurality of channels exits the fill reservoir from the arcuate edge ofthe fill reservoir and extends in a direction normal to a tangent of thearcuate edge for a first portion of the length of the channel, andwherein the plurality of channels are aligned with a longitudinal axisfor a second portion of the length of the channel. The fill reservoiralso includes an axis of symmetry with a fill port proximate the axis ofsymmetry and two or more vent ports arranged symmetrically about theaxis of symmetry. The two or more vent ports are located on a side ofthe vent port that is opposite from the side on which the channels arelocated. The vent ports are in fluid communication with the fillreservoir through vent channels, with the vent channels connected to thefill reservoir at points symmetrical with the axis of symmetry. The fillreservoir also includes outer edges distal from the axis of symmetry anda selectively varied height between two sides of the fill reservoir, andwherein the height of the fill reservoir proximate the outer edges isgreater than the height of the fill reservoir proximate the axis ofsymmetry such that a desired distribution of the volume of the fillreservoir is provided.

[0034] In other aspect, the present invention provides methods ofprocessing sample materials using the sample processing devicesdescribed herein that includes loading the fill reservoir with samplematerial and rotating the sample processing device about an axis ofrotation located proximate a center defined by the arcuate edge of thefill reservoir and the first portions of the channels (if present),whereby the sample material is distributed to the plurality of processchambers.

[0035] These and other features and advantages of the present inventionare described below in connection with various illustrative embodimentsof the devices and methods of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0036]FIG. 1 is a top plan view of the top side of one sample processingdevice of the invention.

[0037]FIG. 2 is a bottom plan view of the bottom side of the body of thesample processing device depicted in FIG. 1 (with a portion of the basesheet removed to expose a portion of the bottom side of the body).

[0038]FIG. 3 is an enlarged cross-sectional view of a portion of thesample processing device of FIG. 1 depicting process chambers,compression structures and a portion of the frame.

[0039]FIG. 4 is an enlarged cross-sectional view of an alternativeprocess chamber incorporating a lens.

[0040]FIG. 5 is an enlarged cross-sectional view of a portion of thesample processing device of FIG. 1 including a fill reservoir and aportion of a channel used to distribute sample material from the fillreservoir to the process chambers.

[0041]FIG. 6 is an enlarged cross-sectional view of an occluded channelin accordance with the principles of the present invention.

[0042]FIG. 7 is the view of FIG. 5 in which a portion of a wallseparating the fill reservoir from an adjacent fill reservoir has beenremoved to place the fill reservoirs in fluid communication with eachother.

[0043]FIG. 8 is a cross-sectional view of an alternative sampleprocessing device including a fill reservoir with a fluid pathway to anadjacent fill reservoir.

[0044]FIG. 9 is a side elevational view of an alternative sampleprocessing device depicting one technique of sealing fill reservoirs.

[0045]FIG. 10 is a block diagram of one thermal processing system thatmay be used in connection with the sample processing devices of thepresent invention.

[0046]FIGS. 11A & 11B depict one example of a frangible element for acompression structure of the present invention.

[0047]FIGS. 12A & 12B depict another example of a frangible element fora compression structure of the present invention.

[0048]FIG. 13 depicts another example of a frangible chromic indicatorfor a compression structure of the present invention.

[0049]FIG. 14 is a perspective view of a preferred form factor for asample processing device according to the present invention.

[0050]FIG. 15 is a plan view of another alternative sample processingdevice according to the present invention.

[0051]FIG. 16 is a cross-sectional view of the fill reservoir of thesample processing device of FIG. 15, taken along line 16-16 in FIG. 15.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE INVENTION

[0052] The present invention provides a sample processing device thatcan be used in the processing of liquid sample materials (or samplematerials entrained in a liquid) in multiple process chambers to obtaindesired reactions, e.g., PCR amplification, ligase chain reaction (LCR),self-sustaining sequence replication, enzyme kinetic studies,homogeneous ligand binding assays, and other chemical, biochemical, orother reactions that may, e.g., require precise and/or rapid thermalvariations. The sample processing devices include one or more fillreservoirs, a plurality of process chambers, and at least one channelplacing the process chambers in fluid communication with a fillreservoir.

[0053] One illustrative sample processing device manufactured accordingto the principles of the present invention is illustrated in FIGS. 1 and2, where FIG. 1 is a plan view of one major side of the sampleprocessing device 10 and FIG. 2 is a plan view of the opposing majorside of the sample processing device 10.

[0054] The side depicted in FIG. 1 will be described as the top side andthe side depicted in FIG. 2 will be described as the bottom side, but itshould be understood that relative positional terms such as “top” and“bottom” are used herein only to indicate that the two sides are onopposite sides of the sample processing device 10. Those terms shouldnot be construed as limiting the present invention. For example, the topside as seen in FIG. 1 may actually be located beneath the bottom sideas seen in FIG. 2 when the device is in actual use to process samplematerial.

[0055] The sample processing device 10 as seen in FIG. 1 includes afirst edge 11 and an opposing second edge 13. A frame 14 extends aroundthe perimeter of the sample processing device 10. Although the frame 14is depicted as extending around the entire perimeter of the sampleprocessing device 10, it should be understood that the frame 14 may beprovided in the form of discontinuous segments that, taken as a whole,assist in defining the perimeter of the sample processing device 10.

[0056] The frame 14 also includes a sides 12 and 15 on which a bar codeor other indicia can be located to assist in identifying the sampleprocessing device 10 and/or its contents during use. The opposing sides12 and 15 can, together, provide opposed parallel planar surfaces thatfacilitate gripping and manipulation of the sample processing device 10by, e.g., a fingers of a user, a robotic manipulator, etc.

[0057] Also seen in FIG. 1 are fill ports 62 used to load samplematerials into the fill reservoirs (described further below) that, inthe depicted embodiment, are located within the frame 14.

[0058] The process chambers 50 are distributed over the top side of thesample processing device 10 within the perimeter of the sampleprocessing device 10, which, in the case of the depicted embodiment, iswithin the boundaries of the frame 14. It may be preferred that theprocess chambers 50 be arranged in a rectilinear grid array as shown tofacilitate interrogation and/or monitoring of the process chambers 50.

[0059] Also depicted in FIG. 1 are the compression structures 70 locatedwithin the array of process chambers 50. As discussed herein, thecompression structures 70 may provide one or more of a number ofdifferent functions. For example, the compression structures 70 may beused to transfer force from the top side of the sample processing device10 to the bottom side of the sample processing device 10, they may beused to equilibrate the applied force over the array of process chambers50, they may be used to provide an indication that the sample processingdevice 10 has been used, etc.

[0060] It may be preferred that the compression structures 70 bedistributed throughout the array of process chambers 50 such thatsubstantially all of the process chambers 50 are located near at leastone compression structure 70. For the purposes of the present invention,“near” will be defined as located with no more than one process chamber50 between the process chamber 50 of interest and the closestcompression structure 70. In the case of a sample processing device 10in which the process chambers 50 are arranged in a rectilinear array,the compression structures 70 and process chambers 50 may be arrangedsuch that all of the process chambers 50 are located adjacent at leastone compression structure (with the possible exception of those fourprocess chambers 50 located at the extreme corners of the array whichare located “near” a compression structure 70). It may be preferred thatthe process chambers 50 are each equidistant from at least onecompression structure 70.

[0061] By distributing the compression structures 70 over the array ofprocess chambers 50, uniformity in the processing of sample materialswithin the process chambers may be enhanced.

[0062]FIG. 2 depicts the bottom side of the body of the sampleprocessing device 10. The sample processing device 10 will typicallyinclude a base sheet 20 attached to the bottom side of the body 30, withthe base sheet 20 being located over substantially all of the bottomside of the body 30. Because the base sheet 30 may typically be opaque,a substantial portion of it is removed in FIG. 2 so that the featuresformed in the bottom side of the body 30 can be seen.

[0063] Fill reservoir structures 60 can be seen in FIG. 2 locatedproximate the edge 11 of the sample processing device 10. Fill ports 62used to load sample material in the fill reservoir structures 60 can beseen within the fill reservoir structures 60. The fill reservoirstructures 60 depicted in FIG. 2 are only one embodiment of a fillreservoir structure that may be used in connection with a sampleprocessing device of the present invention.

[0064] As described in connection with FIG. 2, the various features aredefined as “structures” with the understanding that, until the basesheet 30 is attached to the bottom side of the body 30, the variousstructures do not completely form their respective features. Forexample, until the base sheet 30 is attached, the fill reservoirstructures 60 as seen in FIG. 2 do not form a completed fill reservoir.It may be preferred that all of the structures forming the fillreservoirs 60, process chambers 50, main channels 40 and feeder channels42 be formed into the bottom side of the body 30 while the base sheet 20is provided in the form of a generally flat sheet.

[0065] Each of the fill reservoir structures 60 is in fluidcommunication with a main channel structure 40 that extends away fromthe fill reservoir structure 60 in the general direction of the opposingedge 13. The main channel structure 40 leads to feeder channelstructures 42 that, in turn, lead to a process chamber structure 50.Each of the main channel structures 40 leads to multiple process chamberstructures 50.

[0066] Together, each collection of a fill reservoir structure 60, mainchannel structure 40, feeder channel structures 42, and process chamberstructures 50 can be described as forming a process array on the sampleprocessing device 10. It may be preferred that, as depicted in FIG. 2,each of the process arrays include only one fill reservoir structure 60and only one main channel structure 40. It may be preferred that thefill reservoir volume, i.e., the volume defined by the fill reservoir(if so provided), be equal to or greater than the combined volume of themain channel 40, process chambers 50, and feeder conduits 42 (if any).If desired, each of the process arrays may also include an optionaldrain chamber (not shown) located at the end of the main channel 40opposite the fill reservoir 60.

[0067] In the depicted embodiment, the fill reservoirs 60 are locatedwithin the volume defined by the frame 14. Locating the fill reservoirswithin that volume may provide a number of advantages. For example, thefill reservoirs 60 may be more robust, i.e., be less susceptible todamage during handling, the sample processing device 10 may be morecompact, etc.

[0068] Another advantage of locating the fill reservoirs 60 within thevolume of the frame 14 is that fill ports 62 (see FIG. 1) are alsolocated within the frame 14. By locating the fill ports 62 within theframe 14, more precise control over the location and size of the fillports 62 may be obtained because of the rigidity provided by a structuresuch as a frame 14. That increased control may be particularlyadvantageous if the sample processing device 10 is to be used withautomated filling equipment that requires precise control over thelocation of the fill ports 62.

[0069] The sample processing device 10 includes at least one, andpreferably a plurality of process arrays. Each of the depicted processarrays extends from proximate a first edge 11 towards the second edge 13of the sample processing device 10. The process arrays are depicted asbeing substantially parallel in their arrangement on the sampleprocessing device 10. Although this arrangement may be preferred, itwill be understood that any arrangement of process arrays mayalternatively be provided.

[0070] Alignment of the process arrays may be important if the mainchannels 40 of the process arrays are to be closed simultaneously asdiscussed in more detail below. Alignment of the process arrays may alsobe important if sample materials are to be distributed throughout thesample processing device by rotation about an axis of rotation proximatethe first edge 111 of the sample processing device 10. When so rotated,any sample material located proximate the first edge 111 is driventoward the second edge 13 by centrifugal forces developed during therotation.

[0071] The fill reservoir 60 may be designed to mate with an externalapparatus (e.g., a pipette, hollow syringe, or other fluid deliveryapparatus) to receive the sample material. The fill reservoir 60 itselfmay define a volume (as depicted). Alternatively, the fill reservoir maydefine no specific volume, but, instead, be a location at which samplematerial is to be introduced. For example, the fill reservoir 60 may bemerely a fluid path or port through which a pipette or needle is to beinserted.

[0072] Although the depicted fill reservoirs 60 include fill ports 62,it should be understood that the fill ports 62 are optional. It may bepreferred to provide loading structures that do not include pre-formedfill ports. In such a device, sample material may be introduced into thefill reservoir by piercing the fill reservoir with, e.g., a syringe. Itmay be desirable to use the syringe or another device to pierce the fillreservoir in a one location before piercing the fill reservoir in asecond location to fill the reservoir. The first opening can then serveas a vent port to allow air (or any other gas) within the fill reservoirto escape during loading of the sample material. It may also bepreferred to have multiple fill ports in each fill reservoir, with atleast one fill port functioning as a vent during the loading process.

[0073] After loading, it may be preferred that the fill ports 62 besealed by to prevent leakage of the sample material. One example of asuitable seal mechanism may be, e.g., a pressure sensitive adhesivetape.

[0074] Each of the process arrays in the sample processing devices 10 ofthe present invention may preferably be unvented. As used in connectionwith the present invention, an “unvented” process array is a processarray in which the only ports leading into the volume of the processarray are located in a fill reservoir of the process array. In otherwords, to reach the process chambers within an unvented process array,sample materials must be delivered through the fill reservoir.Similarly, any air or other fluid located within the process arraybefore loading with sample material must also escape from the processarray through the fill reservoir. In contrast, a vented process arraywould include at least one opening outside of the fill reservoir. Thatopening would allow for the escape of any air or other fluid locatedwithin the process array during distribution of the sample materialwithin the process array.

[0075] Methods of distributing sample materials by rotating a sampleprocessing device about an axis of rotation located proximate theloading structures are described in U.S. patent application Ser. No.09/710,184, filed Nov. 10, 2000, titled CENTRIFUGAL FILLING OF SAMPLEPROCESSING DEVICES; U.S. patent application Ser. No. 09/895,001, filedJun. 28, 2001, and titled SAMPLE PROCESSING DEVICES AND CARRIERS(corresponding to International Publication No. WO 02/01181 A2(Bedingham et al.); and U.S. patent application Ser. No. 09/895,010,filed Jun. 28, 2001, and titled SAMPLE PROCESSING DEVICES (correspondingto International Publication No. WO 02/01180 A2 (Bedingham et al.).

[0076] It may be preferred that, regardless of the exact method used todeliver sample materials to the process chambers through the mainchannels of sample processing devices of the present invention, theresult may be that substantially all of the process chambers, mainchannel, and feeder channels (if any) are filled with the samplematerial.

[0077] The process arrays depicted in FIG. 2 are arranged with theprocess chambers 50 located in two groups on both sides of each of themain channels 40. Many different variations in the arrangement of theprocess chambers 50, main channels 40 and feeder channels 42 aredescribed in U.S. patent application Ser. No. 09/710,184, filed Nov. 10,2000, titled CENTRIFUGAL FILLING OF SAMPLE PROCESSING DEVICES; U.S.patent application Ser. No. 09/895,001, filed Jun. 28, 2001, and titledSAMPLE PROCESSING DEVICES AND CARRIERS (corresponding to InternationalPublication No. WO 02/01181 A2 (Bedingham et al.); and U.S. patentapplication Ser. No. 09/895,010, filed Jun. 28, 2001, and titled SAMPLEPROCESSING DEVICES (corresponding to International Publication No. WO02/01180 A2 (Bedingham et al.).

[0078] It may be preferred to maintain the size of the main channels 40and the feeder channels 42 as small as possible while still allowing foradequate sample material delivery and sufficient distance between theprocess chambers 50 to limit diffusion. Reducing the size of thechannels 40 and 42 limits “channel volume” within the process arrays,where channel volume is the combined volume of the main channel 40 andthe feeder channels 42 (where present), i.e., channel volume does notinclude the volume of the process chambers 50. It may be desirable tolimit the ratio of channel volume to the total process chamber volume(i.e., the combined volume of all of the process chambers in the subjectprocess array) to about 2:1 or less, alternatively about 1:1 or less,1:2 or less, or even 1:3 or less.

[0079] One manner in which channel volume can be limited is to reducethe cross-sectional area of the main channel 40 and/or the feederchannels 42 (if present in the device). It may be possible to providefeeder channels 42 with a smaller cross-sectional area than the mainchannel 40 because of the reduced length of the feeder channels 42 ascompared to the main channel 40 (making flow restriction less of aconcern in the feeder channels).

[0080] Turning now to FIG. 3, which is an enlarged cross-sectional viewof a portion of the sample processing device 10 of FIG. 1 depicting thebody 30 including process chambers 50, compression structures 70 and aportion of the frame 14. A base sheet 20 is attached to the bottom sideof the body 30.

[0081] The compression structures 70 each include a peak 72 that isdistal from the bottom side of the body 30. In the depicted embodiment,the compression structures 72 include one or more ribs 74, with themajority of compression structures 70 including four ribs 74 thatdistribute a force applied on the peak of the compression structure overa wider area on the bottom side of the body 30. In FIG. 3, the rib 74extending out of the paper is shown in partial cross-section.

[0082] In a sample processing device 10 that includes a frame 14, it maybe preferred that the compression structures extend above or protrudefrom a plane that is defined by the uppermost surface of the frame 14.In FIG. 3, the peaks 72 of the compression structures 70 are located adistance (d) above the frame 14 (or the plane defined by the frame 14).By extending above the frame 14 or any other structure on the sampleprocessing device 10, the compression structures 70 are assured ofcontacting, e.g., a platen or other device used to force the base sheet20 against, e.g., a thermal block.

[0083] Pairs of adjacent process chambers 50 that are not separated fromeach other by a rib 74 of one of the compression structures 70 areseparated from each other on the top side of the body by a wall 80. Inthe depicted embodiment, a series of walls 80 are provided in arectilinear grid array (see, e.g., FIG. 1) that can perform a variety offunctions.

[0084] Some of the walls 80 may be aligned opposite the main channels 40on the bottom side of the body 30 to provide additional rigidity to thebody during staking or closure of the channels as described in moredetail below. The grid of walls 80 may provide additional rigidity tothe body as a whole in addition to providing support above the mainchannels 40.

[0085] The walls 80 may optionally provide some measure of isolation toreduce optical cross-talk between process chambers 50 by providing abarrier to the transmission of electromagnetic energy (e.g., light)between the process chambers 50 during processing and/or interrogationof the process chambers 50. For example, the walls 80 may be opaque toelectromagnetic radiation of selected wavelengths. Alternatively, thewalls may merely inhibit the transmission of electromagnetic radiationof selected wavelengths by diffusion and/or absorption. For example, thewalls 80 may include textured surfaces to enhance scattering, the walls80 may include materials incorporated into the body of the wall 80and/or provided in a coating thereon that enhance absorption and/ordiffusion of selected wavelengths of electromagnetic energy.

[0086] Each of the process chambers 50 may include a reagent 54. It maybe preferred that at least some, and preferably all, of the processchambers 50 in the devices 10 of the present invention contain at leastone reagent before any sample material is distributed. The reagent 54may be fixed within the process chamber 50 as depicted in FIG. 3. Thereagent 54 is optional, i.e., sample processing devices 10 of thepresent invention may or may not include any reagents 54 in the processchambers 50. In another variation, some of the process chambers 50 mayinclude a reagent 54, while others do not. In yet another variation,different process chambers 50 may contain different reagents.

[0087] The process chamber 50 also defines a volume. In sampleprocessing devices of the present invention, it may be preferred thatthe volume of the process chambers be about 5 microliters or less,alternatively about 2 microliters or less, and, in yet anotheralternative, about 1 microliter or less. Providing sample processingdevices with micro-volume process chambers may be advantageous to reducethe amount of sample material required to load the devices, reducethermal cycling time by reducing the thermal mass of the samplematerials, etc.

[0088] Each of the process chambers 50 includes a window 52 throughwhich materials in the process chamber 50 may be interrogated and/ormonitored. Referring to FIG. 4, an alternative process chamber 150formed by a body 130 and a base sheet 120 is depicted and includes awindow 152 that is shaped to focus electromagnetic energy entering theprocess chamber 150 and/or to collimate or focus electromagnetic energyexiting the process chamber 150 through window 152. As a result, thewindow 152 operates as a lens. In some instances, separate lenses may beinsert-molded into the sample processing device as a part of eachprocess chamber.

[0089] The sample processing devices may also include one or morefeatures to facilitate optical interrogation of the process chambers byan associated instrument platform. Those features may include, e.g.,pins or recesses that align with corresponding structures on theinstrument, optical elements integrated with the process chambers whichmodify the optical path between the instrument and chemistries withinthe chambers, texturing or coloration of areas surrounding the processchambers which reduce optical “cross-talk” between adjacent chambers,etc.

[0090] The body 30 of the sample processing device 10 may bemanufactured of any suitable material or materials. Examples of suitablematerials include moldable materials, e.g., polymeric materials (such aspolypropylene, polyester, polycarbonate, polyethylene, etc.), ceramicmaterials, metals, etc. It may, for example, be preferred that the body30 be manufactured by injection molding of a polymeric material.

[0091] The base sheet 20 can be, e.g., a sheet of metal foil, polymericmaterial, multi-layer composite, etc. that is attached to the bottomside of the body 30 to complete formation of the process array features.It may be preferred that the materials selected for both the body 30 andthe base sheet 20 exhibit good water barrier properties. It may bepreferred that the materials selected for the base sheet 20 bedeformable.

[0092] It may be preferred that at least one of the body 30 and the basesheet 20 be constructed of a material or materials that substantiallytransmit electromagnetic energy of selected wavelengths. For example, itmay be preferred that one or both of the body 30 and the base sheet 20be constructed of materials that allow for visual or machine monitoringof fluorescence and/or color changes within the process chambers 50.

[0093] It may also be preferred that at least one of the body 30 and thebase sheet 20 include a metallic layer, e.g., a metallic foil. If ametallic foil is used to form the base sheet 20, a passivation layer maybe provided on at least the surfaces of the base sheet 20 that face theinteriors of the fill reservoirs 60, main channels 40, feeder channels42, and/or process chambers 50 to prevent contamination of the samplematerials by the metal.

[0094] As an alternative to a separate passivation layer, any adhesivelayer 22 used to attached the base sheet 20 to the body 30 may alsoserve as a passivation layer to prevent contact between the samplematerials and any metals in the base sheet 20. The adhesive may also bebeneficial in that it may be conformable. If so, the adhesive mayprovide enhanced occlusion by filling and/or sealing irregularities orsurface roughness present on the body 30 or the base sheet 20.

[0095] In the illustrative embodiment of the sample processing devicedepicted in FIG. 3, the body 30 may be injection molded polypropyleneand the base sheet 20 may be a metallic foil, e.g., an aluminum or othermetal foil. The metallic foil is preferably deformable as discussed inmore detail herein.

[0096] In the depicted embodiment, the base sheet 20 is attached to thebody 30 using a layer of adhesive 22. In place of adhesive 22, however,the body 30 and base sheet 20 may be attached to each other by anysuitable technique or techniques, e.g., melt bonding, combinations ofmelt bonding and adhesives, etc. As used herein, a “melt bond” is a bondformed by the melting and/or mixing of materials such as that occurringduring, e.g., heat sealing, thermal welding, ultrasonic welding,chemical welding, solvent bonding, etc. If melt bonded, it may bepreferred that both the body 30 and the base sheet 20 include, e.g.,polypropylene or some other melt bondable material at their interface tofacilitate melt bonding.

[0097] It may, however, be preferred that the base sheet 20 be attachedto the body 30 using adhesive. As depicted in FIG. 3, the adhesive maypreferably be provided in the form of a layer 22. It may be preferredthat the adhesive layer 22 be provided as a continuous, unbroken layerover the surface of at least one of the body 30 and the base sheet 20.It may, for example, be preferred that the adhesive layer 22 be providedon the base sheet and, more particularly, it may be preferred that theadhesive layer 22 cover substantially all of the surface of the basesheet 20 facing the body 30.

[0098] A variety of adhesives may be used, although any adhesiveselected should be capable of withstanding the forces generated duringprocessing of any sample materials located in the process chambers 50,e.g., forces developed during distribution of the sample materials,forces developed during thermal processing of the sample materials, etc.Those forces may be large where e.g., the processing involves thermalcycling as in, e.g., polymerase chain reaction and similar processes. Itmay also be preferred that any adhesives used in connection with thesample processing devices exhibit low fluorescence, be compatible be theprocesses and materials to be used in connection with sample processingdevices, e.g. PCR, etc.

[0099] It may be preferred to use adhesives that exhibit pressuresensitive properties. Such adhesives may be more amenable to high volumeproduction of sample processing devices since they typically do notinvolve the high temperature bonding processes used in melt bonding, nordo they present the handling problems inherent in use of liquidadhesives, solvent bonding, ultrasonic bonding, and the like.

[0100] One well known technique for identifying pressure sensitiveadhesives is the Dahlquist criterion. This criterion defines a pressuresensitive adhesive as an adhesive having a 1 second creep compliance ofgreater than 1×10⁻⁶ cm²/dyne as described in Handbook of PressureSensitive Adhesive Technology, Donatas Satas (Ed.), 2^(nd) Edition, p.172, Van Nostrand Reinhold, New York, N.Y., 1989. Alternatively, sincemodulus is, to a first approximation, the inverse of creep compliance,pressure sensitive adhesives may be defined as adhesives having aYoung's modulus of less than 1×10⁶ dynes/cm². Another well known methodof identifying a pressure sensitive adhesive is that it is aggressivelyand permanently tacky at room temperature and firmly adheres to avariety of dissimilar surfaces upon mere contact without the need ofmore than finger or hand pressure, and which may be removed from smoothsurfaces without leaving a residue as described in Test Methods forPressure Sensitive Adhesive Tapes, Pressure Sensitive Tape Council,(1996). Another suitable definition of a suitable pressure sensitiveadhesive is that it preferably has a room temperature storage moduluswithin the area defined by the following points as plotted on a graph ofmodulus versus frequency at 25° C.: a range of moduli from approximately2×10⁵ to 4×10⁵ dynes/cm² at a frequency of approximately 0.1radian/second (0.017 Hz), and a range of moduli from approximately 2×10⁶to 8×10⁶ dynes/cm² at a frequency of approximately 100 radians/second(17 Hz) (for example see FIGS. 8-16 on p. 173 of Handbook of PressureSensitive Adhesive Technology, Donatas Satas (Ed.), 2^(nd) Edition, VanNostrand Rheinhold, New York, 1989). Any of these methods of identifyinga pressure sensitive adhesive may be used to help identify potentiallysuitable pressure sensitive adhesives for use in the methods of thepresent invention.

[0101] It may be preferred that the pressure sensitive adhesives used inconnection with the sample processing devices of the present inventioninclude materials which ensure that the properties of the adhesive arenot adversely affected by water. For example, the pressure sensitiveadhesive will preferably not lose adhesion, lose cohesive strength,soften, swell, or opacify in response to exposure to water during sampleloading and processing. Also, the pressure sensitive adhesive should notcontain any components which may be extracted into water during sampleprocessing, thus possibly compromising the device performance.

[0102] In view of these considerations, it may be preferred that thepressure sensitive adhesive be composed of hydrophobic materials. Assuch, it may be preferred that the pressure sensitive adhesive becomposed of silicone materials. That is, the pressure sensitive adhesivemay be selected from the class of silicone pressure sensitive adhesivematerials, based on the combination of silicone polymers and tackifyingresins, as described in, for example, “Silicone Pressure SensitiveAdhesives”, Handbook of Pressure Sensitive Adhesive Technology, 3^(rd)Edition, pp. 508-517. Silicone pressure sensitive adhesives are knownfor their hydrophobicity, their ability to withstand high temperatures,and their ability to bond to a variety of dissimilar surfaces.

[0103] The composition of the pressure sensitive adhesives is preferablychosen to meet the stringent requirements of the present invention. Somesuitable compositions may be described in International Publication WO00/68336 titled SILICONE ADHESIVES, ARTICLES, AND METHODS (Ko et al.).

[0104] Other suitable compositions may be based on the family ofsilicone-polyurea based pressure sensitive adhesives. Such compositionsare described in U.S. Pat. No. 5,461,134 (Leir et al.); U.S. Pat. No.6,007,914 (Joseph et al.); International Publication No. WO 96/35458(and its related U.S. patent application Ser. No. 08/427,788 (filed Apr.25, 1995); Ser. No. 08/428,934 (filed Apr. 25, 1995); Ser. No.08/588,157 (filed Jan. 17, 1996); and Ser. No. 08/588,159 (filed Jan.17, 1996); International Publication No. WO 96/34028 (and its relatedU.S. patent application Ser. No. 08/428,299 (filed Apr. 25, 1995); Ser.No. 08/428,936 (filed Apr. 25, 1995); Ser. No. 08/569,909 (filed Dec. 8,1995); and Ser. No. 08/569,877 (filed Dec. 8, 1995)); and InternationalPublication No. WO 96/34029 (and its related U.S. patent applicationSer. No. 08/428,735 (filed Apr. 25, 1995) and Ser. No. 08/591,205 (filedJan. 17, 1996)).

[0105] Such pressure sensitive adhesives are based on the combination ofsilicone-polyurea polymers and tackifying agents. Tackifying agents canbe chosen from within the categories of functional (reactive) andnonfunctional tackifiers as desired. The level of tackifying agent oragents can be varied as desired so as to impart the desired tackiness tothe adhesive composition. For example, it may be preferred that thepressure sensitive adhesive composition be a tackifiedpolydiorganosiloxane oligurea segmented copolymer including (a) softpolydiorganosiloxane units, hard polyisocyanate residue units, whereinthe polyisocyanate residue is the polyisocyanate minus the -NCO groups,optionally, soft and/or hard organic polyamine units, wherein theresidues of isocyanate units and amine units are connected by urealinkages; and (b) one or more tackifying agents (e.g., silicate resins,etc.).

[0106] Furthermore, the pressure sensitive layer of the sampleprocessing devices of the present invention can be a single pressuresensitive adhesive or a combination or blend of two or more pressuresensitive adhesives. The pressure sensitive layers may result fromsolvent coating, screen printing, roller printing, melt extrusioncoating, melt spraying, stripe coating, or laminating processes, forexample. An adhesive layer can have a wide variety of thicknesses aslong as it meets exhibits the above characteristics and properties. Inorder to achieve maximum bond fidelity and, if desired, to serve as apassivation layer, the adhesive layer should be continuous and free frompinholes or porosity.

[0107] Even though the sample processing devices may be manufacturedwith a pressure sensitive adhesive to connect the various components,e.g., sides, together, it may be preferable to increase adhesion betweenthe components by laminating them together under elevated heat and/orpressure to ensure firm attachment of the components and sealing of theprocess arrays.

[0108]FIG. 5 depicts a cross-sectional view of a portion of the sampleprocessing device 10 including a fill reservoir 60 formed between thebody 30 and the base sheet 20 (which is attached to the body 30 usingadhesive 22). Also seen in FIG. 5 are a fill port 62 for loading thefill reservoir and a cavity 15 in the body 30 to reduce the thermal massof the body 30.

[0109] A compression structure 70 is depicted and includes a peak 72 anda single rib 74 (which can be contrasted from the multi-ribbedcompliances structures located within the array). As discussed withrespect to FIG. 3, it may be preferred that the compression structures70 extend above or protrude from a plane that is defined by theuppermost surface of the frame 14. The peaks 72 of the compressionstructures 70 are located a distance (d) above the frame 14 (or theplane defined by the frame 14). By extending above the frame 14 or anyother structure on the sample processing device 10, the compressionstructures 70 are assured of contacting, e.g., a platen or other deviceused to urge the base sheet 20 against, e.g., a thermal block or onoptical interrogation device.

[0110]FIG. 5 also depicts a main channel 40 in fluid communication withthe fill reservoir 60. The main channel 40 is formed, in the depictedembodiment, primarily within the body 30, with the base sheet 20 locatedover the main channel structure to define the volume of the channel 40.Also seen in FIG. 5 is a feeder channel 42 extending off of the mainchannel 40.

[0111] Referring to FIG. 6, a cross-sectional view of a main channel 40is depicted to illustrate another potential feature of the sampleprocessing devices of the invention, namely a deformable seal that maybe used to close the main channel 40, isolate the process chambers 50,or accomplish both closure of the main channel 40 and isolation of theprocess chambers 50.

[0112] The main channel 40 is sealed or occluded by forcing the basesheet 20 into the channel 40. In some instances, the material of thebase sheet 20 will undergo plastic deformation. In other instances, theadhesive 22 alone may be enough to retain the base sheet 20 in contactwith the surface of the channel 40 sufficiently to occlude the channel40 (with the base sheet 20 undergoing only elastic deformation). Anyconformability in the adhesive 22 may allow it to conform and/or deformto more completely fill and occlude the channel being occluded. It maybe preferred that the adhesive 22 be a pressure sensitive adhesive,although a hot melt adhesive may alternatively be used if deformation ofthe base sheet 20 is accompanied by the application of thermal energysufficient to activate the hot melt adhesive.

[0113] It should be understood that complete sealing or occlusion of thedeformed portions of the sample processing device 10 may not berequired. For example, it may only be required that the deformationrestrict flow, migration or diffusion through a conduit or other fluidpathway sufficiently to provide the desired isolation. As used inconnection with the present invention, “occlusion” will include bothpartial occlusion and complete occlusion (unless otherwise explicitlyspecified).

[0114] As used in connection with the present invention, the deformableseals may be provided in a variety of locations and/or structuresincorporated into the sample processing devices. Essentially, however,the deformable seal in a process array will be located somewhere in thefluid path between the loading chamber and the plurality of processchambers. Occlusion of the main channel may be continuously oversubstantially all of the length of the main channel or it may beaccomplished over discrete portions or locations along the length of themain channel. Also, closure of the deformable seal may be accomplishedby occlusion of the feeder channels alone and/or by occlusion of thefeeder channel/main channel junctions (in place of, or in addition to,occlusion of a portion or all of the length of the main channel).

[0115] With respect to FIG. 1, for example, the deformable seal may belocated in the main channel 40 between the fill reservoir 60 and theprocess chambers 50 of each process array. In this configuration thedeformable seal may extend for the substantially the entire length ofthe main channel 40 or it may be limited to selected areas. For example,the deformable seal may extend along the main channel 40 only in theareas occupied by the feeder channels 42 leading to the process chambers50. In another example, the deformable seal may be a composite structureof discrete sealing points located along the main channel 40 or withineach of the feeder channels 42. In another configuration, the deformableseal may be limited to the area between the fill reservoirs 60 and theprocess chambers 50 in each of the process arrays.

[0116] In some embodiments it may be advantageous to occlude the mainchannel over substantially all of its length and, in so doing, urge anysample materials within the main channel back towards the fill reservoir60. It may be preferred that the sample materials urged back towards thefill reservoir are driven back into the fill reservoir. As a result, thefill reservoirs in process arrays of the present invention may alsoserve as waste or purge chambers for sample materials urged out of themain channels and/or feeder channels during closure of the deformableseals.

[0117]FIGS. 7 & 8 depict variations in the fill reservoir structures.Referring first to FIG. 7, the fill reservoir 60 of FIG. 5 is depictedwith an fluid path 64 provided in the common wall that the reservoirshares with its adjacent fill reservoir (see, e.g., FIG. 2). The fluidpath 64 can be formed by removing a portion of the wall such that thetwo fill reservoirs are no longer isolated from each other, therebyproviding a common fill reservoir for two process arrays on the sampleprocessing device 10. Removal of the wall portion may be accomplishedby, e.g., using a forceps, pliers or other device or technique. Thismethod will typically be accomplished by removing the portion before thebase sheet 20 is attached to the body 30.

[0118] The fill reservoir 160 of FIG. 8 includes a fluid path 164 formedin the wall between what would otherwise be two isolated fillreservoirs. In this embodiment, the opening may be occluded by adeformable seal as described above with the respect to the channels. Inother words, the fill reservoir structures may be isolated from eachother by forcing the base sheet 120 into the fluid path 164 such thatthe fluid path 164 is occluded. In this manner, a sample processingdevice in which fill reservoir structures are in fluid communicationwith each other may be customized by selectively occluding the fluidpaths between the fill reservoir structures. For example, all of thefill reservoirs 60 located along edge 11 of the sample processing device10 in FIG. 1 may be in fluid communication through fluid paths similarto fluid path 164. The fill reservoirs 60 may then be selectivelyisolated to provide a customized sample processing device according tothe present invention.

[0119]FIG. 9 is a side elevational view of a portion of another sampleprocessing device according to the present invention. The sampleprocessing device 210 includes a body 230 and a base sheet 220 that, inthe depicted embodiment, is attached to the body 230 by a layer ofadhesive 222. The body includes a frame 214 and compression structures270 extending above the frame 214.

[0120] One difference between the sample processing device 210 and thesample processing device 10 described above is that the base sheet 220extends past the boundaries or footprint of the body 230. As a result,the base sheet 220 can be wrapped around the frame 214 of the body 230to, e.g., seal any fill ports (not shown in FIG. 9) that lead into fillreservoirs (also not shown in FIG. 9). This sealing technique may beused in place of, e.g., a separate adhesive tape as discussed above.

[0121] Although the base sheet 220 is depicted as including a continuouslayer of adhesive 222, it will be understood that the base sheet 220 maybe attached to the bottom of body 230 by any suitable technique(adhesive or otherwise). It will also be understood that the adhesiveused to attach the base sheet extension (i.e., that portion of the basesheet 220 that extends beyond the body 230) to the upper side of thebody 230 may be the same adhesive (as shown) or a different adhesive.Although not shown, a release liner may be provided to protect theadhesive 222 before it is used to seal the fill ports.

[0122]FIG. 10 depicts one thermal processing system that may be used inconnection with the sample processing devices of the present inventionin a block diagram format. The system includes an sample processingdevice 110 located on a platform 108, which may be, e.g., a thermalblock. If platform 108 is a thermal block, the temperature of theplatform 108 is preferably controlled by a thermal controller 106. Onthe opposite side of the sample processing device 110, a platen 104 isprovided to urge the sample processing device 110 into intimate contactwith the platform 108. The temperature of the platen 104 may bethermally controlled (if desired) by a thermal controller 102 (that may,in some instances, be the same as a controller 106 controlling thetemperature of the thermal block 108). The sample processing device 110is compressed between the platen 104 and platform 108 as indicated byarrows 101 and 102 during thermal processing of the sample processingdevice 110.

[0123] In alternative systems, the block 108 may, instead, be an opticalinterrogation platform 108 against which the sample processing device110 is urged to improve optical coupling of the process chambers in thesample processing device 110 with the optical components in theinterrogation platform 108. In such a system, the sample processingdevice 110 would preferably include a base sheet that transmits theelectromagnetic energy used for interrogation. The interrogationplatform 108 may be in optical or other communication with aninterrogation system controller 106. Such an interrogation system may beused for “end-point reads” if the sample processing device 110 isprocessed using, e.g., thermal sinks such as fluid baths or othersystems that do not include a thermal block and/or do not provide forintegrated interrogation of the sample processing device 110.

[0124] As discussed above, the compression structures of the sampleprocessing devices of the present invention may provide a variety ofdifferent functions. FIGS. 11A & 11B depict an isolated view of oneembodiment of a compression structure 270 that includes a ridge 272.FIG. 11B illustrates the ridge 272 after permanent deformation.

[0125] The ridge 272 is one form of a frangible element located on acompression structure in accordance with the present invention. Theridge 272 may preferably be constructed to permanently deform upon theapplication of sufficient pressure by, e.g., a platen. That deformationcan provide a number of functions. For example, it can provide anindication that the sample processing device on which the compressionstructure 270 is located has been used. The deformation can also providesome level of equilibration in the applied forces. For example,manufacturing tolerances may result in different heights betweendifferent compression structures. Those variations may, however, bemoderated by varying deformation of the ridges 272 on differentcompression structures 270.

[0126] In other words, taller compression structures may experience moredeformation, while shorter compression structures may experience lessdeformation. It may be preferred that the dimensions of the compressionstructures be selected such that all of the compression structures willexperience at least some deformation to ensure that all of thecompression structures are used to transmit force to the base sheet ofthe sample processing devices. In other words, the compressionstructures may improve compliance of the sample processing device,thereby enabling better thermal contact to the heating platen.

[0127]FIGS. 12A & 12B depict another example of a frangible element 372on a compression structure, with FIG. 12A depicting the frangibleelement 372 before deformation and FIG. 12B depicting the frangibleelement 372 after deformation.

[0128]FIG. 13 depicts another frangible element 472 on a compressionstructure 470. The frangible element 472 may include a chromicindicator, e.g., beads, etc. that rupture under pressure or areotherwise modified such that a color change occurs after the applicationof pressure on the compression structure 470.

[0129]FIG. 14 depicts the form factor that a sample processing deviceaccording to the present invention may preferably take. It may bepreferred that the height (h) of the sample processing devices of theinvention comply with the height requirements as discussed by theSociety for Biomolecular Screening Standard “SBS-2 forMicroplates—Height Dimensions” (May 9, 2002). That standard sets forth amaximum height of 14.35 millimeters (±0.25 millimeters). At the lowerend of the range, it may be preferred that the height of sampleprocessing devices according to the present invention be 5 millimetersor more. A minimum height may be beneficial to assist in handling of thesample processing devices by, e.g., robotic handling systems.

[0130] It may also be preferred that the footprint dimensions, that isthe length (l) and the width (w) comply with the footprint requirementsas discussed by the Society for Biomolecular Screening Standard “SBS-1for Microplates—Footprint Dimensions” (Jan. 17, 2002). That standardsets forth a length of 127.76 millimeters (±0.25 millimeters) and awidth of 85.48 millimeters (±0.25 millimeters). Unlike the heightdimension, it may not be desirable to provide sample processing deviceswith a significantly different footprint because most, if not all,conventional microplate processing systems are designed to processdevices with the footprint identified above. Although conventionalsystems may readily use sample processing devices that do not reach themaximum height specified in the standard, they may not be readilyadaptable for use with devices having a different footprint.

[0131]FIG. 15 is a plan view of a portion of another alternative sampleprocessing device 510 according to the present invention and FIG. 16 isa cross-sectional view taken along line 16-16 in FIG. 15. Only a portionof the sample processing device 510 is seen in the figures, with thebase sheet 520 extending past the footprint of the body 530 along oneedge of the body 530 (see, e.g., FIG. 9 above for a side elevationalview of a similar base sheet extension). A cover 530 a is attached tothe base sheet 520 where it extends past the body 530.

[0132] In this embodiment, the base sheet 520 and cover 530 a may be,e.g., a laminated construction similar to those described in, e.g., U.S.patent application Ser. No. 09/895,001, filed 28 Jun. 2001, and titledSAMPLE PROCESSING DEVICES AND CARRIERS (corresponding to InternationalPublication No. WO 02/01181 A2 (Bedingham et al.); and U.S. patentapplication Ser. No. 09/895,010, filed 28 Jun. 2001, and titled SAMPLEPROCESSING DEVICES (corresponding to International Publication No. WO02/01180 A2 (Bedingham et al.). As a result, one or both of thelaminated layers can be formed to provide a volume therebetween. In thedepicted embodiment, that cover 530 a is formed to provide a fillreservoir 560, funnels 541, and channels 540 a and 540 b that lead tothe main channels (not shown) formed within the bounds of the body 530as discussed above. Alternatively, the features may be formed in thebase sheet 520 or in both the cover 530 a and the base sheet 520.

[0133] The single fill reservoir 560 is used to load multiple mainchannels in the sample processing device 510. It may be preferred thatthe sample processing device 510 include only one fill reservoir 560,although more than one fill reservoir feeding two or more channels maybe used in connection with the present invention.

[0134] The fill reservoir 560 and associated channels are designed in amanner that may provide several advantages if the sample materials areto be loaded into the process chambers of the sample processing deviceusing centrifugal forces. For example, the arcuate edge 566 of the fillreservoir 560 may preferably be designed to follow a circular arc havinga radius defined by the location of the axis of rotation 501 about whichsample processing device 510 is rotated to deliver sample materials fromthe fill reservoir 560 to the channels. Minor variations from a truecircular arc may be tolerated within the scope of the invention unlessotherwise specified. That arcuate edge design may, for example, resultin a radial vector alignment of the liquid flow front as it enters thefunnels 541 feeding the channels 540 a to provide essentially uniformflow into all channels due to the balanced hydrostatic equilibrium alongthe curved edge 566 of the fill reservoir 560. In contrast, a fillreservoir with a flat front edge (i.e., the edge facing away from theaxis of rotation 501) may experience fluid starvation to one or morechannels during loading by centrifugation.

[0135] Another feature of the design depicted in FIG. 15 is theorientation of the funnels 541 and channels 540 a that are in directfluid communication with the fill reservoir 560. As discussed above, theedge 566 of the fill reservoir 560 may preferably have a curvaturedefined by the axis of rotation 501. To further promote even flow ofsample material out of the fill reservoir 560, each of the channels 540a (and associated option funnels 541) exits the fill reservoir 560 fromthe arcuate edge 566 and may preferably be aligned radially with respectto the axis of rotation 501. As a result, the channels 540 a are normalto a tangent of the arcuate edge 566 of the fill reservoir 560. Onepotential advantage of this arrangement is that the fluid force vectorsdeveloped during centrifugation about the axis 501 are aligned with thechannels 540 a, further enhancing even flow out of the fill reservoir560.

[0136] The radially-aligned channels 540 a may, however, preferablytransition to channels 540 b that are generally aligned with alongitudinal axis 511 to match the arrangement of main channels (notshown) within the body 530 of the sample processing device 510. Thosemain channels are, as described above, preferably parallel with eachother to facilitate staking or closure of the main channels to reducefluid movement between process chambers during processing.

[0137] The larger fill reservoir 560 may include support structures 580within its boundaries to prevent collapse during handling andprocessing. The support structures 580 may be elongated as shown (i.e.,have a length greater than their width) or take any other desired shape.The elongated support structures 580 may be aligned with thelongitudinal axis 511 of the sample processing device 510 or they mayalternatively be aligned radially as are channels 540 a (i.e., normal toa tangent of the arcuate edge 566). As depicted in FIG. 16 (across-sectional view of FIG. 15 taken along line 16-16), the supportstructures 580 may be formed in the cover 530 a forming the fillreservoir 560 if it is of the laminated construction discussed above. Inany design, however, the support structures are provided as intermediatesupport within the boundaries of the fill reservoir 560 to, e.g., reducethe likelihood of collapse of the fill reservoir 560 due to handling orsuction forces that may develop during distribution of the samplematerial from the fill reservoir to the process chambers in the device510.

[0138] Another feature depicted in FIG. 15 is fill port 562 that may beused to load sample material into the fill reservoir 560. Also seen inFIG. 15 are vent ports 561 connected to the main portion of the fillreservoir 560 by vent channels 563. The fill reservoir 560 preferablyhas a shape and construction that is symmetrical about the longitudinalaxis 511 of the sample processing device 510. The symmetrical fillreservoir 560 also preferably includes a fill port 562 that is locatedalong the longitudinal axis 511 of the sample processing device 510.

[0139] Multiple vent ports 561 are preferably provided in the fillreservoir 560 in a symmetrical arrangement with respect to the fill port562 and the overall shape of the fill reservoir 560. It may be preferredthat the vent ports 561 be located proximate the longitudinal axis 511of the sample processing device 510 to along vent channels 563 that openinto the main body of the fill reservoir 560 at points arrangedsymmetrically with respect to the longitudinal axis 511 (which is alsothe axis of symmetry for the fill reservoir 560). Another feature of thevent ports 561 is that they are preferably located on the opposite sideof the fill port 562 with respect to the channels 540 a to, e.g., reducethe likelihood of leakage from the vent ports 561 during centrifugalloading.

[0140] Isolating the vent ports 563 from the main portion of the fillreservoir 560 may reduce or eliminate leakage of sample material fromthe vent ports 561 during handling of the sample processing device 510.Also, the symmetric nature of the vent ports 561 and vent channels 563may enhance even loading of sample material into the fill reservoir 560and even fluid flow out of the fill reservoir 560 during centrifugationof the sample processing device 510.

[0141] As an alternative to, or in addition to the arcuate edge designfor the fill reservoir 560, the height of the reservoir between the twosides of the fill reservoir may also be selectively varied such that adesired distribution of the volume of the fill reservoir is provided.That volumetric distribution can then be used to achieve a correspondingdistribution of fluid sample material within the fill reservoir to,e.g., cause the sample material to pool preferentially towards the outeredges of the device.

[0142] This feature is illustrated in the cross-sectional view of FIG.16, wherein the height of the fill reservoir 560 is greater proximatethe outer edges of the fill reservoir 560 (i.e., distal from the centerof the fill reservoir 560) than the height of the reservoir 560proximate its center. That feature may be particularly useful if thefill reservoir is symmetric about an axis (such as axis 511 as seen inFIG. 15). The increased volume of the fill reservoir 560 proximate itsouter edges may reduce or prevent fluid starvation that could hindereven filling of all of the distribution channels in a sample processingdevice of the present invention.

[0143] This same concept, i.e., fill reservoirs with differentialvolumes may be used in connection with any sample processing deviceaccording to the present invention. For example, if the fill reservoirs60 in the sample processing device 10 of FIGS. 1 & 2 are in fluidcommunication with each other (as described above, e.g., in connectionwith FIGS. 7 & 8) the fill reservoirs 60 may preferably be provided withdifferent volumes to reduce fluid starvation in the outermost reservoirs60. For example, the outermost fill reservoirs 60 (those closest tosides 12 and 15) may be larger in volume than the fill reservoirs 60closer to the center of the fill reservoir structure. Further, the fillreservoirs 60 may be designed such that any fluid within the fillreservoirs 60 is preferentially distributed towards the outermost fillreservoirs 60 when the sample processing device 10.

[0144] Patents, patent applications, and publications disclosed hereinare hereby incorporated by reference as if individually incorporated. Itis to be understood that the above description is intended to beillustrative, and not restrictive. Various modifications and alterationsof this invention will become apparent to those skilled in the art fromthe foregoing description without departing from the scope of thisinvention, and it should be understood that this invention is not to beunduly limited to the illustrative embodiments set forth herein.

1. A method of processing sample materials, the method comprising:providing a sample processing device comprising a body that comprises afirst major side and a second major side; a base sheet attached to thefirst major side of the body, and a plurality of compression structuresprotruding from the second major side of the body, wherein the body andthe base sheet define one or more fill reservoirs, a plurality ofprocess chambers, and a plurality of channels, wherein each channel ofthe plurality of channels is in fluid communication with at least onefill reservoir of the one or more fill reservoirs, and wherein eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels;distributing sample material to at least some process chambers of theplurality of process chambers; locating the base sheet of the sampleprocessing device in contact with a thermal block; contacting the secondmajor side of the body with a platen to urge the base sheet of thesample processing device into intimate contact with the thermal block;permanently deforming at least some of the plurality of compressionstructures protruding from the second major side of the body whilecontacting the second major side of the body with the platen;controlling the temperature of the thermal block while the sampleprocessing device is in contact with the thermal block.
 2. A methodaccording to claim 1, wherein permanently deforming the plurality ofcompression structures protruding from the second major side of the bodywhile contacting the second major side of the body with the platencomprises permanently deforming all of the plurality of compressionstructures on the body.
 3. A method according to claim 1, wherein eachcompression structure of the plurality of compression structurescomprises a post extending from the first major surface to the secondmajor surface of the body, wherein contacting the second major side ofthe body with a platen to urge the base sheet of the sample processingdevice into intimate contact with the thermal block transfers force fromthe platen to the thermal block.
 4. A method according to claim 1,wherein permanently deforming at least some of the plurality ofcompression structures comprises permanently deforming a frangibleindicator element on the permanently deformed compression structures. 5.A method according to claim 1, wherein permanently deforming at leastsome of the plurality of compression structures comprises changing thecolor of a chromic indicator on the permanently deformed compressionstructures.
 6. A method according to claim 1, wherein the body comprisesa frame proximate a perimeter of the body, the frame defining a frameplane proximate the second major surface of the body, wherein theplurality of compression structures protrude from the frame planeproximate the second major surface of the body.
 7. A method according toclaim 1, wherein the device comprises a plurality of fill reservoirs,and wherein at least one pair of adjacent fill reservoirs is in fluidcommunication with each other, and further wherein the method comprisesisolating the at least one pair of adjacent fill reservoirs such thatthe at least one pair of adjacent fill reservoirs are no longer in fluidcommunication with each other.
 8. A method according to claim 7, whereinisolating the at least one pair of adjacent fill reservoirs comprisespermanently deforming the base sheet to occlude a fluid path.
 9. Amethod according to claim 8, wherein the fluid path is formed in thefirst major surface of the body.
 10. A method according to claim 1,wherein the body comprises a frame proximate a perimeter of the body,the frame defining a frame volume, and wherein the one or more fillreservoirs are located within the frame volume.
 11. A method accordingto claim 1, wherein the one or more fill reservoirs comprises two ormore fill reservoirs in fluid communication with each other, wherein atleast two of the fill reservoirs have a different volume.
 12. A methodof processing sample materials, the method comprising: providing asample processing device comprising a body that comprises a first majorside and a second major side; a base sheet attached to the first majorside of the body, and a plurality of compression structures protrudingfrom the second major side of the body, wherein the body and the basesheet define one or more fill reservoirs, a plurality of processchambers, and a plurality of channels, wherein each channel of theplurality of channels is in fluid communication with at least one fillreservoir of the one or more fill reservoirs, and wherein each processchamber of the plurality of process chambers is in fluid communicationwith at least one channel of the plurality of channels, and wherein thebody comprises a frame proximate a perimeter of the body, the framedefining a frame volume, wherein the one or more fill reservoirs arelocated within the frame volume; distributing sample material to atleast some process chambers of the plurality of process chambers;locating the base sheet of the sample processing device in contact witha thermal block; contacting the second major side of the body with aplaten to urge the base sheet of the sample processing device intointimate contact with the thermal block; permanently deforming all ofthe compression structures protruding from the second major side of thebody while contacting the second major side of the body with the platen;controlling the temperature of the thermal block while the sampleprocessing device is in contact with the thermal block; wherein eachcompression structure of the plurality of compression structurescomprises a post extending from the first major surface to the secondmajor surface of the body, wherein contacting the second major side ofthe body with a platen to urge the base sheet of the sample processingdevice into intimate contact with the thermal block transfers force fromthe platen to the thermal block; and wherein permanently deforming theplurality of compression structures comprises permanently deforming afrangible indicator element on at least some of the plurality ofcompression structures.
 13. A method of interrogating a sampleprocessing device, the method comprising: providing a sample processingdevice comprising a body that comprises a first major side and a secondmajor side; a base sheet attached to the first major side of the body,and a plurality of compression structures protruding from the secondmajor side of the body, wherein the body and the base sheet define aplurality of process chambers with sample material located in at leastsome process chambers of the plurality of process chambers; locating thebase sheet of the sample processing device in contact with aninterrogation platform; contacting the second major side of the bodywith a platen to urge the base sheet of the sample processing deviceinto intimate contact with the interrogation platform; permanentlydeforming at least some of the plurality of compression structuresprotruding from the second major side of the body while contacting thesecond major side of the body with the platen; and interrogating atleast some of the process chambers while the sample processing device isin contact with the interrogation platform.
 14. A method according toclaim 13, wherein permanently deforming the plurality of compressionstructures protruding from the second major side of the body whilecontacting the second major side of the body with the platen comprisespermanently deforming all of the plurality of compression structures onthe body.
 15. A method according to claim 13, wherein each compressionstructure of the plurality of compression structures comprises a postextending from the first major surface to the second major surface ofthe body, wherein contacting the second major side of the body with aplaten to urge the base sheet of the sample processing device intointimate contact with the interrogation platform transfers force fromthe platen to the thermal block.
 16. A method according to claim 13,wherein permanently deforming at least some of the plurality ofcompression structures comprises permanently deforming a frangibleindicator element on the permanently deformed compression structures.17. A method according to claim 13, wherein permanently deforming atleast some of the plurality of compression structures comprises changingthe color of a chromic indicator on the permanently deformed compressionstructures.
 18. A method according to claim 13, wherein the bodycomprises a frame proximate a perimeter of the body, the frame defininga frame plane proximate the second major surface of the body, whereinthe plurality of compression structures protrude from the frame planeproximate the second major surface of the body.
 19. A method ofmanufacturing a sample processing device, the method comprising:providing a body that comprises a first major side and a second majorside, a plurality of isolated fill reservoir structures located betweenthe first major side of the body and the second major side of the body;a plurality of process chamber structures formed into the first majorside of the body; and a plurality of channel structures formed into thefirst major side of the body; opening a fluid path between at least onepair of adjacent isolated fill reservoir structures, wherein the numberof isolated fill reservoir structures is reduced; attaching a base sheetto the first major side of the body, wherein the body and the base sheetdefine one or more fill reservoirs, a plurality of process chambersstructures, and a plurality of channels, wherein each channel of theplurality of channels is in fluid communication with at least one fillreservoir of the one or more fill reservoirs, and wherein each processchamber of the plurality of process chambers is in fluid communicationwith at least one channel of the plurality of channels.
 20. A methodaccording to claim 19, wherein the at least one pair of adjacentisolated fill reservoir structures comprises a common wall separatingthe at least one pair of adjacent isolated fill reservoir structures,and wherein opening the fluid path comprises removing at least a portionof the common wall.
 21. A method according to claim 19, wherein the bodycomprises a plurality of compression structures protruding from thesecond major side of the body.
 22. A method according to claim 21,wherein each compression structure of the plurality of compressionstructures comprises a post extending from the first major surface tothe second major surface of the body, wherein contacting the secondmajor side of the body with a platen to urge the base sheet of thesample processing device into intimate contact with a platform transfersforce from the platen to the platform.
 23. A method according to claim19, wherein each compression structure of the plurality of compressionstructures comprises a frangible indicator element.
 24. A methodaccording to claim 19, wherein each compression structure of theplurality of compression structures comprises a chromic indicator.
 25. Amethod according to claim 19, wherein the body comprises a frameproximate a perimeter of the body, the frame defining a frame planeproximate the second major surface of the body, wherein a plurality ofcompression structures protrude from the frame plane proximate thesecond major surface of the body.
 26. A method according to claim 19,wherein the body comprises a frame proximate a perimeter of the body,the frame defining a frame volume, and wherein the one or more fillreservoirs are located within the frame volume.
 27. A method accordingto claim 19, wherein the one or more fill reservoirs comprises two ormore fill reservoirs in fluid communication with each other, wherein atleast two of the fill reservoirs have a different volume.
 28. A methodaccording to claim 19, wherein each process chamber of the plurality ofprocess chambers comprises a lens formed in the body.
 29. A sampleprocessing device comprising: a body that comprises a first major sideand a second major side; one or more fill reservoir structures locatedbetween the first major side of the body and the second major side ofthe body; a plurality of process chamber structures formed into thefirst major side of the body; a plurality of channel structures formedinto the first major side of the body; a plurality of compressionstructures protruding from the second major side of the body, whereinthe plurality of compression structures comprise frangible indicatorelements proximate the second major side of the body; and a base sheetattached to the first major side of the body, wherein the base sheet andthe one or more fill reservoir structures define one or more fillreservoirs in the device, wherein the base sheet and the plurality ofprocess chamber structures define a plurality of process chambers in thedevice, and wherein the base sheet and the plurality of channelstructures define a plurality of channels in the device, wherein eachchannel of the plurality of channels is in fluid communication with atleast one fill reservoir of the one or more fill reservoirs, and whereineach process chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels.30. A device according to claim 29, wherein each compression structureof the plurality of compression structures comprises a post extendingfrom the first major surface to the second major surface of the body,wherein contacting the second major side of the body with a platen tourge the base sheet of the sample processing device into intimatecontact with the thermal block transfers force from the platen to thethermal block.
 31. A device according to claim 29, wherein the frangibleindicator element comprises a chromic indicator that changes color whenpermanently deformed.
 32. A device according to claim 29, wherein thebody comprises a frame proximate a perimeter of the body, the framedefining a frame plane proximate the second major surface of the body,wherein the plurality of compression structures protrude from the frameplane proximate the second major surface of the body.
 33. A deviceaccording to claim 29, wherein the body comprises a frame proximate aperimeter of the body, the frame defining a frame volume, and whereinthe one or more fill reservoirs are located within the frame volume. 34.A device according to claim 29, wherein the one or more fill reservoirscomprises two or more fill reservoirs in fluid communication with eachother, wherein at least two of the fill reservoirs have a differentvolume.
 35. A device according to claim 29, wherein the device comprisesa plurality of fill reservoirs, and wherein at least one pair ofadjacent fill reservoirs is in fluid communication with each otherthrough a fluid path proximate the first major side of the body.
 36. Adevice according to claim 29, wherein each process chamber of theplurality of process chambers comprises a lens formed in the body.
 37. Asample processing device comprising: a fill reservoir; a plurality ofprocess chambers; and a plurality of channels, wherein each channel ofthe plurality of channels is in fluid communication with the fillreservoir and wherein each process chamber of the plurality of processchambers is in fluid communication with at least one channel of theplurality of channels; wherein the fill reservoir comprises an arcuateedge, wherein each channel of the plurality of channels exits the fillreservoir from the arcuate edge of the fill reservoir, wherein eachchannel of the plurality of channels extends in a direction normal to atangent of the arcuate edge for a first portion of the length of thechannel, and wherein the plurality of channels are aligned with alongitudinal axis for a second portion of the length of the channel. 38.A device according to claim 37, wherein the fill reservoir comprises anaxis of symmetry, and wherein the fill reservoir comprises: a fill portproximate the axis of symmetry; and two or more vent ports arrangedsymmetrically about the axis of symmetry.
 39. A device according toclaim 38, wherein the vent ports are in fluid communication with thefill reservoir through vent channels, with the vent channels connectedto the fill reservoir at points symmetrical with the axis of symmetry.40. A device according to claim 37, wherein the fill reservoir comprisesa fill port and one or more vent ports, and further wherein the one ormore vent ports are located on a side of the fill reservoir that isopposite from the side on which the channels are located.
 41. A deviceaccording to claim 37, further comprising one or more support structureslocated within the fill reservoir, wherein the support structuresmaintain spacing between two opposing sides of the fill reservoir.
 42. Adevice according to claim 41, wherein the support structures areelongated and arranged along a direction normal to a tangent of thearcuate edge.
 43. A device according to claim 37, wherein the fillreservoir comprises a selectively varied height between two sides of thefill reservoir such that a desired distribution of the volume of thefill reservoir is provided.
 44. A device according to claim 43, whereinthe fill reservoir comprises a center and outer edges distal from thecenter, and wherein the height of the fill reservoir proximate the outeredges is greater than the height of the fill reservoir proximate thecenter.
 45. A device according to claim 37, wherein each channel of theplurality of channels is in fluid communication with the arcuate edge ofthe fill reservoir through a funnel.
 46. A sample processing devicecomprising: a fill reservoir; a plurality of process chambers; and aplurality of channels, wherein each channel of the plurality of channelsis in fluid communication with the fill reservoir and wherein eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels;wherein the fill reservoir comprises an axis of symmetry, and whereinthe fill reservoir comprises a fill port proximate the axis of symmetry;and two or more vent ports arranged symmetrically about the axis ofsymmetry.
 47. A device according to claim 46, wherein the vent ports arein fluid communication with the fill reservoir through vent channels,with the vent channels connected to the fill reservoir at pointssymmetrical with the axis of symmetry.
 48. A device according to claim46, wherein the fill reservoir comprises a fill port and one or morevent ports, and further wherein the one or more vent ports are locatedon a side of the vent port that is opposite from the side on which thechannels are located.
 49. A device according to claim 46, furthercomprising one or more support structures located within the fillreservoir, wherein the support structures maintain spacing between twoopposing sides of the fill reservoir.
 50. A device according to claim46, wherein the fill reservoir comprises a selectively varied heightbetween two sides of the fill reservoir such that a desired distributionof the volume of the fill reservoir is provided.
 51. A device accordingto claim 46, wherein the fill reservoir comprises outer edges distalfrom the axis of symmetry, and wherein the height of the fill reservoirproximate the outer edges is greater than the height of the fillreservoir proximate the axis of symmetry.
 52. A sample processing devicecomprising: a fill reservoir; a plurality of process chambers; and aplurality of channels, wherein each channel of the plurality of channelsis in fluid communication with the fill reservoir and wherein eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels;wherein the fill reservoir comprises a selectively varied height betweentwo sides of the fill reservoir such that a desired distribution of thevolume of the fill reservoir is provided.
 53. A device according toclaim 52, wherein the fill reservoir comprises a center and outer edgesdistal from the center, and wherein the height of the fill reservoirproximate the outer edges is greater than the height of the fillreservoir proximate the center.
 54. A device according to claim 52,wherein the fill reservoir comprises a fill port and one or more ventports, and further wherein the one or more vent ports are located on aside of the vent port that is opposite from the side on which thechannels are located.
 55. A device according to claim 52, furthercomprising one or more support structures located within the fillreservoir, wherein the support structures maintain spacing between twoopposing sides of the fill reservoir.
 56. A sample processing devicecomprising: a fill reservoir; a plurality of process chambers; and aplurality of channels, wherein each channel of the plurality of channelsis in fluid communication with the fill reservoir and wherein eachprocess chamber of the plurality of process chambers is in fluidcommunication with at least one channel of the plurality of channels;one or more support structures located within the fill reservoir,wherein the support structures maintain spacing between two opposingsides of the fill reservoir; wherein the fill reservoir comprises anarcuate edge, wherein each channel of the plurality of channels exitsthe fill reservoir from the arcuate edge of the fill reservoir andextends in a direction normal to a tangent of the arcuate edge for afirst portion of the length of the channel, and wherein the plurality ofchannels are aligned with a longitudinal axis for a second portion ofthe length of the channel; and wherein the fill reservoir comprises anaxis of symmetry, and wherein the fill reservoir comprises a fill portproximate the axis of symmetry; and two or more vent ports arrangedsymmetrically about the axis of symmetry, wherein the two or more ventports are located on a side of the vent port that is opposite from theside on which the channels are located; and further wherein the ventports are in fluid communication with the fill reservoir through ventchannels, with the vent channels connected to the fill reservoir atpoints symmetrical with the axis of symmetry; and still further whereinthe fill reservoir comprises outer edges distal from the axis ofsymmetry and a selectively varied height between two sides of the fillreservoir, and wherein the height of the fill reservoir proximate theouter edges is greater than the height of the fill reservoir proximatethe axis of symmetry such that a desired distribution of the volume ofthe fill reservoir is provided.
 57. A method of processing samplematerials, the method comprising: providing a sample processing deviceaccording to claim 37; loading the fill reservoir with sample material;rotating the sample processing device about an axis of rotation locatedproximate a center defined by the arcuate edge of the fill reservoir andthe first portions of the channels, whereby the sample material isdistributed to the plurality of process chambers.
 58. A method ofprocessing sample materials, the method comprising: providing a sampleprocessing device according to claim 56; loading the fill reservoir withsample material; rotating the sample processing device about an axis ofrotation located proximate a center defined by the arcuate edge of thefill reservoir and the first portions of the channels, whereby thesample material is distributed to the plurality of process chambers.